Guideline for Treating Motor Symptoms of PD Gets First Update Since 2002

The American Academy of Neurology (AAN) updated 2002 guidelines regarding the treatment of motor symptoms with dopaminergic medications in patients with early-stage Parkinson disease (PD), which has no disease-modifying therapy.

The guidelines, published in Neurology, the journal of the AAN, were created by a multidisciplinary panel after a systematic review of the latest evidence. They searched Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from database inception through June 2020 for relevant peer-reviewed articles, ultimately selecting 59 for the final analysis.

The guideline reflects the panel’s findings regarding confidence in evidence statements about how to care for the motor symptoms in patients with early PD, including the comparative efficacy of treatments as well as the comparative risk of adverse events.

Motor symptoms in the early stages of PD include tremor, rigidity, and bradykinesia. Treatment options include dopaminergic medications, which either increase dopamine levels or mimic dopamine effects. They include levodopa, a drug that is converted into dopamine in the brain; dopamine agonists, drugs that mimic the effects of dopamine; and monoamine oxidase B (MAO-B) inhibitors, drugs that prevent an enzyme called MAO-B from breaking down dopamine.

Each therapy carries its own risk and benefit, the guidelines note. Levodopa is superior at reducing motor symptoms compared with either dopamine agonists or MAO-B inhibitors.

However, the guideline also found that initial treatment with levodopa is more likely than using dopamine agonists as the first treatment to cause adverse effects, specifically dyskinesia, during the first 5 years of treatment.

Because the prevalence of severe or disabling dyskinesia was also low during the first 5 years, the guideline also recommends that neurologists prescribe the lowest effective dose of levodopa to optimize benefit and minimize the risk of dyskinesia.

The panel also reviewed evidence about different forms of these medications, and said that from an efficacy standpoint, long-acting forms of levodopa and levodopa with entacapone do not appear to differ from immediate-release levodopa, although there may be different reasons clinicians and patients may prefer one form over another.

Likewise, the comparison of different formulations of dopamine agonists showed little evidence that any one formulation or method of administration is better than another.

However, dopamine agonists have their own pitfalls, the guideline notes, as they are more likely than levodopa to cause impulse-control disorders such as compulsive gambling, eating, shopping, or sexual activity, as well as hallucinations. They are also linked with a greater risk of excessive daytime sleepiness, making them problematic for patients with jobs that require driving or operating heavy machinery.

Patients may not always report these nonmotor symptoms out of embarrassment, the guideline notes.

Patients are more likely to stop their treatment due to adverse effects when taking dopamine agonists and MAO-B inhibitors, compared with taking levodopa, the guideline said.

In addition, individuals taking MAO-B inhibitors were more likely to require additional therapy within 2 to 3 years.

The report concludes with recommendations for future research directions, including, among others, starting disease-modifying therapy early, once such a therapy exists; considering the role of genetic status in order to advance precision medicine; and determining whether newer methods of providing stable levodopa plasma levels started soon after diagnosis will delay the onset of dyskinesia.

Reference

Pringsheim T, Day GS, Smith DB, et al. Dopaminergic therapy for motor symptoms in early Parkinson disease practice guideline summary: a report of the AAN guideline subcommittee. Neurology. 2021;97(20):942-957. doi:10.1212/WNL.0000000000012868